The nasal epithelia of vertebrates play important roles in the detection of chemical cues in our environment such as odorants related to food, sexual and non-sexual social interaction, predators, and hazards. The common view attributes ciliated receptor neurons to the main olfactory epithelium to detect mainly food odors and microvillous receptor neurons to the vomeronasal organ to detect sexual/social cues. The respiratory epithelium was said to contain only free nerve endings of the trigeminal nerve to detect potentially noxious substances. However, recent studies as well as our preliminary data show that morphology and function of the nasal epithelia are more complex. Our preliminary data indicate that the main olfactory epithelium of rodents and humans contains receptor cells that do not match the description of ciliated receptor neurons and that the respiratory epithelium contains several types of sensory cells. As these cells occur in considerable numbers (e.g. microvillous cells in the main olfactory epithelium > 5%), they represent a physiologically relevant population whose function may play an important role in chemosensation. Based on my preliminary data, I hypothesize that the main olfactory epithelia of humans and rodents contain unconventional cells such as the crypt olfactory receptor neuron hitherto only described for fish and that the respiratory epithelia contain several types of solitary chemosensory cells. The goal of this proposal is to characterize these unconventional receptor cells. My experiments are designed to obtain a clear picture of their anatomical and biochemical features to enable future functional experiments. Well-established immunocytochemical and ultrastructural (scanning and transmission electron microscopy) techniques on human and rodent nasal tissue will be utilized to determine the neuronal properties and morphological characteristics of these cells. Taken together, these experiments will render a more detailed knowledge of the sensory cell types present in the nasal epithelia, and thus, facilitate further studies on their function. A thorough knowledge of the cell types involved in the detection of odorants is critical in order to understand disorders and diseases of the olfactory system, such as anosmia caused by head trauma or cancer treatment, Alzheimer's or Parkinsonian diseases and to conceive possible remedies.